IRF5-mediated immune responses and its implications in immunological disorders

References

• Suresh R, Mosser DM, Ablasser A, Bauernfeind F, Hartmann G, Latz E, et al. Pattern recognition receptors in innate immunity, host defense, and immunopathology. Adv Physiol Educ. 2013 Dec;37(4):284–291. doi:10.1152/advan.00058.2013.
   PubMed Web of Science ®Google Scholar
• Chaplin DD. Overview of the immune response. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S3. doi:10.1016/j.jaci.2009.12.980. PMID:20176265.
   PubMed Web of Science ®Google Scholar
• Singh H, Khan AA, Dinner AR, et al. Gene regulatory networks in the immune system. Trends Immunol. 2014 May;35(5):211–218. doi:10.1016/j.it.2014.03.006.
   PubMed Web of Science ®Google Scholar
• Taniguchi T, Ogasawara K, Takaoka A, Tanaka N. IRF family of transcription factors as regulators of host defense. Annu Rev Immunol. 2001 Jan;19:623–655. doi:10.1146/annurev.immunol.19.1.623.
   PubMed Web of Science ®Google Scholar
• Miyamoto M, Fujita T, Kimura Y, et al. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi:10.1016/S0092-8674(88)91307-4.
   PubMed Web of Science ®Google Scholar
• Tamura T, Yanai H, Savitsky D, Taniguchi T. The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol. 2008 Jan 27;26:535–584. doi:10.1146/annurev.immunol.26.021607.090400.
   PubMed Web of Science ®Google Scholar
• Lee H-R, Kim MH, Lee J-S, Liang C, Jung JU. Viral interferon regulatory factors. J Interferon Cytokine Res. 2009 Sep;29(9):621–627. doi:10.1089/jir.2009.0067.
   PubMed Web of Science ®Google Scholar
• Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol. 2006 Sep;6(9):644–658. doi:10.1038/nri1900.
   PubMed Web of Science ®Google Scholar
• Honda K, Takaoka A, Taniguchi T. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity. 2006 Sep;25(3):349–360. doi:10.1016/j.immuni.2006.08.009.
   PubMed Web of Science ®Google Scholar
• Battistini A. Interferon regulatory factors in hematopoietic cell differentiation and immune regulation. J Interf Cytokine Res. 2009 Dec;29(12):765–780. doi:10.1089/jir.2009.0030.
   PubMed Web of Science ®Google Scholar
• Zhao G-N, Jiang D-S, Li H. Interferon regulatory factors: at the crossroads of immunity, metabolism, and disease. Biochim Biophys Acta – Mol Basis Dis. 2015;1852(2):365–378. doi:10.1016/j.bbadis.2014.04.030.
   PubMed Web of Science ®Google Scholar
• Lohoff M, Mak TW. Roles of interferon-regulatory factors in T-helper-cell differentiation. Nat Rev Immunol. 2005 Feb;5(2):125–135. doi:10.1038/nri1552.
   PubMed Web of Science ®Google Scholar
• Barnes BJ, Moore PA, Pitha PM. Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes. J Biol Chem. 2001 Jun 29;276(26):23382–23390. doi:10.1074/jbc.M101216200.
   PubMed Web of Science ®Google Scholar
• Barnes BJ, Kellum MJ, Field AE, Pitha PM. Multiple regulatory domains of IRF-5 control activation, cellular localization, and induction of chemokines that mediate recruitment of T lymphocytes. Mol Cell Biol. 2002 Aug;22(16):5721–5740. 1128/MCB.22.16.5721-5740.2002.
   PubMed Web of Science ®Google Scholar
• Takaoka A, Yanai H, Kondo S, et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature. 2005 Mar 10;434(7030):243–249. doi:10.1038/nature03308.
   PubMed Web of Science ®Google Scholar
• Pimenta EM, De S, Weiss R, et al. IRF5 is a novel regulator of CXCL13 expression in breast cancer that regulates CXCR5(+) B- and T-cell traffi cking to tumor-conditioned media. Immunol Cell Biol. 2015 May-Jun;93(5):486–499. doi:10.1038/icb.2014.110.
   PubMed Web of Science ®Google Scholar
• Barnes BJ, Kellum MJ, Pinder KE, Frisancho JA, Pitha PM. Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death. Cancer Res. 2003 Oct 1;63(19):6424–6431.
   PubMed Web of Science ®Google Scholar
• Yanai H, Chen H-M, Inuzuka T, et al. Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3402–3407. doi:10.1073/pnas.0611559104.
   PubMed Web of Science ®Google Scholar
• Massimino M, Vigneri P, Fallica M, et al. IRF5 promotes the proliferation of human thyroid cancer cells. Mol Cancer. 2012;11:21. doi:10.1186/1476-4598-11-21. PMID:22507190.
   PubMed Web of Science ®Google Scholar
• Mancl ME, Hu G, Sangster-Guity N, et al. Two discrete promoters regulate the alternatively spliced human interferon regulatory factor-5 isoforms. Multiple isoforms with distinct cell type-specific expression, localization, regulation, and function. J Biol Chem. 2005 Jun 3;280(22):21078–21090. doi:10.1074/jbc.M500543200.
   PubMed Web of Science ®Google Scholar
• Li D, De S, Li D, Song S, Matta B, Barnes BJ. Specific detection of interferon regulatory factor 5 (IRF5): a case of antibody inequality. Sci Rep. 2016;6:31002. doi:10.1038/srep31002. PMID:27481535.
   PubMed Web of Science ®Google Scholar
• Ishikawa C, Senba M, Barnes BJ, Mori N. Constitutive expression of IRF-5 in HTLV-1-infected T cells. Int J Oncol. 2015 Jul;47(1):361–369. doi:10.3892/ijo.2015.3020.
   PubMed Web of Science ®Google Scholar
• Yamashita M, Toyota M, Suzuki H, et al. DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosae. Cancer Sci. 2010 Jul;101(7):1708–1716. doi:10.1111/j.1349-7006.2010.01581.x.
   PubMed Web of Science ®Google Scholar
• Li Q, Tainsky MA. Epigenetic Silencing of IRF7 and/or IRF5 in lung cancer cells leads to increased sensitivity to oncolytic viruses. Katoh M, editor. PLoS One. 2011 Dec 14;6(12):e28683. doi:10.1371/journal.pone.0028683.
   PubMed Web of Science ®Google Scholar
• Kozyrev S V, Alarcon-Riquelme ME. The genetics and biology of Irf5-mediated signaling in lupus. Autoimmunity. 2007 Dec;40(8):591–601. doi:10.1080/08916930701510905.
   PubMed Web of Science ®Google Scholar
• Clark DN, Read RD, Mayhew V, Petersen SC, Argueta LB, Stutz LA, et al. Four Promoters of IRF5 respond distinctly to stimuli and are affected by autoimmune-risk polymorphisms. Front Immunol. 2013;4:360. doi:10.3389/fimmu.2013.00360. PMID:24223576.
   PubMed Web of Science ®Google Scholar
• Keren H, Lev-Maor G, Ast G. Alternative splicing and evolution: diversification, exon definition and function. Nat Rev Genet. 2010 May 8;11(5):345–355. doi:10.1038/nrg2776.
   PubMed Web of Science ®Google Scholar
• Eames HL, Corbin AL, Udalova IA. Interferon regulatory factor 5 in human autoimmunity and murine models of autoimmune disease. Transl Res. 2016 Jan;167(1):167–182. doi:10.1016/j.trsl.2015.06.018.
   PubMed Web of Science ®Google Scholar
• Wen F, Ellingson SM, Kyogoku C, Peterson EJ, Gaffney PM. Exon 6 variants carried on systemic lupus erythematosus (SLE) risk haplotypes modulate IRF5 function. Autoimmunity. 2011 Mar;44(2):82–89. doi:10.3109/08916934.2010.491842.
   PubMed Web of Science ®Google Scholar
• Lazzari E, Korczeniewska J, Ní Gabhann J, Smith S, Barnes BJ, Jefferies CA. TRIpartite motif 21 (TRIM21) differentially regulates the stability of interferon regulatory factor 5 (IRF5) isoforms. PLoS One. 2014;9(8):e103609. doi:10.1371/journal.pone.0103609. PMID:25084355.
   PubMed Web of Science ®Google Scholar
• Clark DN, Lambert JP, Till RE, et al. Molecular effects of autoimmune-risk promoter polymorphisms on expression, exon choice, and translational efficiency of interferon regulatory factor 5. J Interf Cytokine Res. 2014 May;34(5):354–365. doi:10.1089/jir.2012.0105.
   PubMed Web of Science ®Google Scholar
• Lin R, Yang L, Arguello M, Penafuerte C, Hiscott J. A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization. J Biol Chem. 2005 Jan 28;280(4):3088–3095. doi:10.1074/jbc.M408452200.
   PubMed Web of Science ®Google Scholar
• Korczeniewska J, Barnes BJ. The COP9 signalosome interacts with and regulates interferon regulatory factor 5 protein stability. Mol Cell Biol. 2013 Mar 15;33(6):1124–1138. doi:10.1128/MCB.00802-12.
   PubMed Web of Science ®Google Scholar
• Paun A, Reinert JT, Jiang Z, Medin C, Balkhi MY, Fitzgerald KA, et al. Functional characterization of murine interferon regulatory factor 5 (IRF-5) and its role in the innate antiviral response. J Biol Chem. 2008 May 23;283(21):14295–14308. doi:10.1074/jbc.M800501200.
   PubMed Web of Science ®Google Scholar
• Kristjansdottir G, Sandling JK, Bonetti A, et al. Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations. J Med Genet. 2008 Jun;45(6):362–369. doi:10.1136/jmg.2007.055012.
   PubMed Web of Science ®Google Scholar
• Carmona FD, Martin J-E, Beretta L, et al. The systemic lupus erythematosus irf5 risk haplotype is associated with systemic sclerosis. Kuwana M, editor. PLoS One. 2013 Jan 23;8(1):e54419. doi:10.1371/journal.pone.0054419.
   PubMed Web of Science ®Google Scholar
• Miceli-Richard C, Gestermann N, Ittah M, et al. The CGGGG insertion/deletion polymorphism of the IRF5 promoter is a strong risk factor for primary Sjögren's syndrome. Arthritis Rheum. 2009 Jul;60(7):1991–7. doi:10.1002/art.24662.
   PubMedGoogle Scholar
• Sigurdsson S, Nordmark G, Göring HHH, et al. Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J Hum Genet. 2005 Mar;76(3):528–537. doi:10.1086/428480.
   PubMed Web of Science ®Google Scholar
• Graham RR, Kozyrev S V, Baechler EC, et al. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet. 2006 May 16;38(5):550–555. doi:10.1038/ng1782.
   PubMed Web of Science ®Google Scholar
• Alonso-Perez E, Suarez-Gestal M, Calaza M, et al. Cis-regulation of IRF5 expression is unable to fully account for systemic lupus erythematosus association: analysis of multiple experiments with lymphoblastoid cell lines. Arthritis Res Ther. 2011 May 31;13(3):R80. doi:10.1186/ar3343.
   PubMed Web of Science ®Google Scholar
• Sigurdsson S, Göring HHH, Kristjansdottir G, et al. Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for systemic lupus erythematosus. Hum Mol Genet. 2008 Mar 15;17(6):872–881. doi:10.1093/hmg/ddm359.
   PubMed Web of Science ®Google Scholar
• Rullo OJ, Woo JMP, Wu H, et al. Association of IRF5 polymorphisms with activation of the interferon alpha pathway. Ann Rheum Dis. 2010 Mar;69(3):611–617. doi:10.1136/ard.2009.118315.
   PubMed Web of Science ®Google Scholar
• Stone RC, Du P, Feng D, et al. RNA-Seq for enrichment and analysis of irf5 transcript expression in SLE. Tsokos GC, editor. PLoS One. 2013 Jan 18;8(1):e54487. doi:10.1371/journal.pone.0054487.
   PubMed Web of Science ®Google Scholar
• Feng D, Stone RC, Eloranta M-L, et al. Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus. Arthritis Rheum. 2010 Feb;62(2):562–573.
   PubMedGoogle Scholar
• Cunninghame Graham DS, Manku H, Wagner S, et al. Association of IRF5 in UK SLE families identifies a variant involved in polyadenylation. Hum Mol Genet. 2007 Mar 15;16(6):579–591. doi:10.1093/hmg/ddl469.
   PubMed Web of Science ®Google Scholar
• Kozyrev S V, Lewén S, Reddy PMVL, et al. Structural insertion/deletion variation in IRF5 is associated with a risk haplotype and defines the precise IRF5 isoforms expressed in systemic lupus erythematosus. Arthritis Rheum. 2007 Apr;56(4):1234–1241. doi:10.1002/art.22497.
   PubMedGoogle Scholar
• Niewold TB, Kelly JA, Flesch MH, Espinoza LR, Harley JB, Crow MK. Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Arthritis Rheum. 2008 Aug;58(8):2481–2487. doi:10.1002/art.23613.
   PubMed Web of Science ®Google Scholar
• Lazzari E, Jefferies CA. IRF5-mediated signaling and implications for SLE. Clin Immunol. 2014 Aug;153(2):343–352. doi:10.1016/j.clim.2014.06.001.
   PubMed Web of Science ®Google Scholar
• Richez C, Yasuda K, Bonegio RG, Watkins AA, Aprahamian T, Busto P, et al. IFN regulatory factor 5 is required for disease development in the fcgammariib−/−yaa and fcgammaRIIB−/− mouse models of systemic lupus erythematosus. J Immunol. 2010 Jan 15;184(2):796–806. doi:10.4049/jimmunol.0901748.
   PubMed Web of Science ®Google Scholar
• Tada Y, Kondo S, Aoki S, et al. Interferon regulatory factor 5 is critical for the development of lupus in MRL/lpr mice. Arthritis Rheum. 2011 Mar;63(3):738–748. doi:10.1002/art.30183.
   PubMedGoogle Scholar
• Feng D, Yang L, Bi X, Stone RC, Patel P, Barnes BJ. Irf5-deficient mice are protected from pristane-induced lupus via increased Th2 cytokines and altered IgG class switching. Eur J Immunol. 2012 Jun;42(6):1477–1487. doi:10.1002/eji.201141642.
   PubMed Web of Science ®Google Scholar
• Yasuda K, Watkins AA, Kochar GS, et al. Interferon regulatory factor-5 deficiency ameliorates disease severity in the MRL/lpr mouse model of lupus in the absence of a mutation in DOCK2. PLoS One. 2014;9(7):e103478. doi:10.1371/journal.pone.0103478. PMID:25076492.
   PubMed Web of Science ®Google Scholar
• Weiss M, Byrne AJ, Blazek K, et al. IRF5 controls both acute and chronic inflammation. Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):11001–11006. doi:10.1073/pnas.1506254112.
   PubMed Web of Science ®Google Scholar
• Saigusa R, Asano Y, Taniguchi T, et al. Multifaceted contribution of the TLR4-activated IRF5 transcription factor in systemic sclerosis. Proc Natl Acad Sci U S A. 2015 Dec 8;112(49):15136–15141. doi:10.1073/pnas.1520997112.
   PubMed Web of Science ®Google Scholar
• Chen W, Lam SS, Srinath H, et al. Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5. Nat Struct Mol Biol. 2008 Nov;15(11):1213–1220. doi:10.1038/nsmb.1496.
   PubMed Web of Science ®Google Scholar
• Ryzhakov G, Eames HL, Udalova IA. Activation and function of interferon regulatory factor 5. J Interferon Cytokine Res. 2015 Feb;35(2):71–78. doi:10.1089/jir.2014.0023.
   PubMed Web of Science ®Google Scholar
• Feng D, Sangster-Guity N, Stone R, et al. Differential requirement of histone acetylase and deacetylase activities for IRF5-mediated proinflammatory cytokine expression. J Immunol. 2010 Nov 15;185(10):6003–6012. doi:10.4049/jimmunol.1000482.
   PubMed Web of Science ®Google Scholar
• Eames HL, Saliba DG, Krausgruber T, Lanfrancotti A, Ryzhakov G, Udalova IA. KAP1/TRIM28: an inhibitor of IRF5 function in inflammatory macrophages. Immunobiology. 2012 Dec;217(12):1315–1324. doi:10.1016/j.imbio.2012.07.026.
   PubMed Web of Science ®Google Scholar
• Chang Foreman H-C, Van Scoy S, Cheng T-F, et al. Activation of interferon regulatory factor 5 by site specific phosphorylation. Mossman KL, editor. PLoS One. 2012 Mar 8;7(3):e33098. doi:10.1371/journal.pone.0033098.
   PubMed Web of Science ®Google Scholar
• Ren J, Chen X, Chen ZJ. IKKβ is an IRF5 kinase that instigates inflammation. Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17438–17443. doi:10.1073/pnas.1418516111.
   PubMed Web of Science ®Google Scholar
• Lopez-Pelaez M, Lamont DJ, Peggie M, Shpiro N, Gray NS, Cohen P. Protein kinase IKKβ-catalyzed phosphorylation of IRF5 at Ser462 induces its dimerization and nuclear translocation in myeloid cells. Proc Natl Acad Sci. 2014 Dec 9;111(49):17432–17437. doi:10.1073/pnas.1418399111.
   PubMed Web of Science ®Google Scholar
• Ouyang X, Negishi H, Takeda R, Fujita Y, Taniguchi T, Honda K. Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation. Biochem Biophys Res Commun. 2007;354(4):1045–1051. doi:10.1016/j.bbrc.2007.01.090. PMID:17275788.
   PubMed Web of Science ®Google Scholar
• Schoenemeyer A, Barnes BJ, Mancl ME, Latz E, Goutagny N, Pitha PM, et al. The interferon regulatory factor, irf5, is a central mediator of toll-like receptor 7 signaling. J Biol Chem. 2005 Apr 29;280(17):17005–17012. doi:10.1074/jbc.M412584200.
   PubMed Web of Science ®Google Scholar
• Balkhi MY, Fitzgerald KA, Pitha PM. Functional regulation of MyD88-activated interferon regulatory factor 5 by K63-linked polyubiquitination. Mol Cell Biol. 2008 Dec;28(24):7296–7308. doi:10.1128/MCB.00662-08.
   PubMed Web of Science ®Google Scholar
• Pandey AK, Yang Y, Jiang Z, et al. NOD2, RIP2 and IRF5 play a critical role in the type i interferon response to mycobacterium tuberculosis. Cossart P, editor. PLoS Pathog. 2009 Jul 3;5(7):e1000500. doi:10.1371/journal.ppat.1000500.
   PubMed Web of Science ®Google Scholar
• Cushing L, Winkler A, Jelinsky SA, et al. IRAK4 kinase activity controls Toll-like receptor-induced inflammation through the transcription factor IRF5 in primary human monocytes. J Biol Chem. 2017 Sep 10;292(45):18689–18698. doi:10.1074/jbc.M117.796912.
   PubMed Web of Science ®Google Scholar
• Fu B, Zhao M, Wang L, et al. RNAi screen and proteomics reveal nxf1 as a novel regulator of irf5 signaling. Sci Rep. 2017 Dec 2;7(1):2683. doi:10.1038/s41598-017-02857-z.
   PubMedGoogle Scholar
• Lazear HM, Lancaster A, Wilkins C, et al. IRF-3, IRF-5, and IRF-7 Coordinately regulate the type i ifn response in myeloid dendritic cells downstream of mavs signaling. Basler CF, editor. PLoS Pathog. 2013 Jan 3;9(1):e1003118. doi:10.1371/journal.ppat.1003118.
   PubMed Web of Science ®Google Scholar
• del Fresno C, Soulat D, Roth S, et al. Interferon-β production via dectin-1-syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans. Immunity. 2013;38(6):1176–1186. doi:10.1016/j.immuni.2013.05.010. PMID:23770228.
   PubMed Web of Science ®Google Scholar
• Proenca-Modena JL, Hyde JL, Sesti-Costa R, et al. Interferon-regulatory factor 5-dependent signaling restricts orthobunyavirus dissemination to the central nervous system. J Virol. 2016 Jan;90(1):189–205. doi:10.1128/JVI.02276-15.
   PubMed Web of Science ®Google Scholar
• Barnes BJ, Richards J, Mancl M, Hanash S, Beretta L, Pitha PM. Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection. J Biol Chem. 2004 Oct 22;279(43):45194–45207. doi:10.1074/jbc.M400726200.
   PubMed Web of Science ®Google Scholar
• Thackray LB, Shrestha B, Richner JM, et al. Interferon regulatory factor 5-dependent immune responses in the draining lymph node protect against west nile virus infection. J Virol. 2014 Oct;88(19):11007–11021. doi:10.1128/JVI.01545-14.
   PubMed Web of Science ®Google Scholar
• Dai P, Cao H, Merghoub T, et al. Myxoma virus induces type I interferon production in murine plasmacytoid dendritic cells via a TLR9/MyD88-, IRF5/IRF7-, and IFNAR-dependent pathway. J Virol. 2011 Oct;85(20):10814–10825. doi:10.1128/JVI.00104-11.
   PubMed Web of Science ®Google Scholar
• Nandakumar R, Finsterbusch K, Lipps C, et al. Hepatitis C virus replication in mouse cells is restricted by IFN-dependent and -independent mechanisms. Gastroenterology. 2013 Dec 1;145(6):1414–1423.e1. doi:10.1053/j.gastro.2013.08.037.
   PubMed Web of Science ®Google Scholar
• Cevik O, Li D, Baljinnyam E, et al. Interferon regulatory factor 5 (IRF5) suppresses hepatitis C virus (HCV) replication and HCV-associated hepatocellular carcinoma. J Biol Chem. 2017 Dec 29;292(52):21676–21689. doi:10.1074/jbc.M117.792721.
   PubMed Web of Science ®Google Scholar
• Cheng T-F, Brzostek S, Ando O, Van Scoy S, Kumar KP, Reich NC. Differential activation of IFN regulatory factor (IRF)-3 and IRF-5 transcription factors during viral infection. J Immunol. 2006 Jun 15;176(12):7462–7470. doi:10.4049/jimmunol.176.12.7462.
   PubMed Web of Science ®Google Scholar
• Shukla V, Lu R. IRF4 and IRF8: Governing the virtues of B lymphocytes. Front Biol (Beijing). 2014 Aug;9(4):269–282. doi:10.1007/s11515-014-1318-y.
   PubMedGoogle Scholar
• Goodnow CC, Vinuesa CG, Randall KL, Mackay F, Brink R. Control systems and decision making for antibody production. Nat Immunol. 2010 Aug 20;11(8):681–688. doi:10.1038/ni.1900.
   PubMed Web of Science ®Google Scholar
• De S, Zhang B, Shih T, et al. B Cell-Intrinsic role for IRF5 in TLR9/BCR-Induced human b cell activation, proliferation, and plasmablast differentiation. Front Immunol. 2018 Jan 10;8:1938. doi:10.3389/fimmu.2017.01938.
   PubMed Web of Science ®Google Scholar
• Savitsky DA, Yanai H, Tamura T, Taniguchi T, Honda K. Contribution of IRF5 in B cells to the development of murine SLE-like disease through its transcriptional control of the IgG2a locus. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10154–10159. doi:10.1073/pnas.1005599107.
   PubMed Web of Science ®Google Scholar
• De Silva NS, Klein U. Dynamics of B cells in germinal centres. Nat Rev Immunol. 2015 Feb 6;15(3):137–148. doi:10.1038/nri3804.
   PubMed Web of Science ®Google Scholar
• Nutt SL, Hodgkin PD, Tarlinton DM, Corcoran LM. The generation of antibody-secreting plasma cells. Nat Rev Immunol. 2015 Mar 20;15(3):160–171. doi:10.1038/nri3795.
   PubMed Web of Science ®Google Scholar
• Ochiai K, Maienschein-Cline M, Simonetti G, et al. Transcriptional regulation of germinal center b and plasma cell fates by dynamical control of IRF4. Immunity. 2013 May 23;38(5):918–929. doi:10.1016/j.immuni.2013.04.009.
   PubMed Web of Science ®Google Scholar
• Lien C, Fang C-M, Huso D, Livak F, Lu R, Pitha PM. Critical role of IRF-5 in regulation of B-cell differentiation. Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4664–4668. doi:10.1073/pnas.0911193107.
   PubMed Web of Science ®Google Scholar
• Shen H, Panchanathan R, Rajavelu P, Duan X, Gould KA, Choubey D. Gender-dependent expression of murine Irf5 gene: implications for sex bias in autoimmunity. J Mol Cell Biol. 2010 Oct;2(5):284–290. doi:10.1093/jmcb/mjq023.
   PubMed Web of Science ®Google Scholar
• Panchanathan R, Liu H, Liu H, et al. Distinct regulation of murine lupus susceptibility genes by the IRF5/Blimp-1 axis. J Immunol. 2012 Jan 1;188(1):270–278. doi:10.4049/jimmunol.1102311.
   PubMed Web of Science ®Google Scholar
• Fang C-M, Roy S, Nielsen E, et al. Unique contribution of IRF-5-Ikaros axis to the B-cell IgG2a response. Genes Immun. 2012 Jul;13(5):421–430. doi:10.1038/gene.2012.10.
   PubMed Web of Science ®Google Scholar
• Thompson EC, Cobb BS, Sabbattini P, et al. Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits. Immunity. 2007 Mar;26(3):335–344. doi:10.1016/j.immuni.2007.02.010.
   PubMed Web of Science ®Google Scholar
• Kopf M, Herren S, Wiles MV. Pepys mb, kosco-vilbois mh. interleukin 6 influences germinal center development and antibody production via a contribution of c3 complement component. J Exp Med. 1998 Nov 16;188(10):1895–1906. doi:10.1084/jem.188.10.1895.
   PubMed Web of Science ®Google Scholar
• Dienz O, Eaton SM, Bond JP, et al. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells. J Exp Med. 2009 Jan 16;206(1):69–78. doi:10.1084/jem.20081571.
   PubMed Web of Science ®Google Scholar
• Purtha WE, Swiecki M, Colonna M, Diamond MS, Bhattacharya D. Spontaneous mutation of the Dock2 gene in Irf5−/− mice complicates interpretation of type I interferon production and antibody responses. Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):E898–904. doi:10.1073/pnas.1118155109.
   PubMed Web of Science ®Google Scholar
• Guo X, Chen S-Y. Dedicator of cytokinesis 2 in cell signaling regulation and disease development. J Cell Physiol. 2017 Aug;232(8):1931–1940. doi:10.1002/jcp.25512.
   PubMed Web of Science ®Google Scholar
• Yasuda K, Nündel K, Watkins AA, et al. Phenotype and function of B cells and dendritic cells from interferon regulatory factor 5-deficient mice with and without a mutation in DOCK2. Int Immunol. 2013 May;25(5):295–306. doi:10.1093/intimm/dxs114.
   PubMed Web of Science ®Google Scholar
• Yasuda K, Watkins AA, Kochar GS, et al. Interferon regulatory factor-5 deficiency ameliorates disease severity in the MRL/lpr mouse model of lupus in the absence of a mutation in DOCK2. PLoS One. 2014 Jan;9(7):e103478. doi:10.1371/journal.pone.0103478.
   PubMed Web of Science ®Google Scholar
• Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol. 2014 May 23;14(6):392–404. doi:10.1038/nri3671.
   PubMed Web of Science ®Google Scholar
• Feng D, Stone RC, Eloranta M-L, et al. Genetic variants and disease-associated factors contribute to enhanced IRF-5 expression in blood cells of systemic lupus erythematosus patients. Arthritis Rheum. 2010;62(2):NA–NA. doi:10.1002/art.27223.
   Google Scholar
• Stone RC, Feng D, Deng J, et al. Interferon regulatory factor 5 activation in monocytes of systemic lupus erythematosus patients is triggered by circulating autoantigens independent of type I interferons. Arthritis Rheum. 2012 Mar;64(3):788–798. doi:10.1002/art.33395.
   PubMedGoogle Scholar
• Yang L, Feng D, Bi X, Stone RC, Barnes BJ. Monocytes from Irf5−/− mice have an intrinsic defect in their response to pristane-induced lupus. J Immunol. 2012 Oct 1;189(7):3741–3750. doi:10.4049/jimmunol.1201162.
   PubMed Web of Science ®Google Scholar
• Xu Y, Lee PY, Li Y, et al. Pleiotropic IFN-Dependent and -independent effects of IRF5 on the pathogenesis of experimental lupus. J Immunol. 2012 Apr 15;188(8):4113–4121. doi:10.4049/jimmunol.1103113.
   PubMed Web of Science ®Google Scholar
• Bergstrøm B, Aune MH, Awuh JA, et al. TLR8 Senses staphylococcus aureus rna in human primary monocytes and macrophages and induces IFN-β Production via a TAK1-IKKβ-IRF5 signaling pathway. J Immunol. 2015 Aug 1;195(3):1100–1111. doi:10.4049/jimmunol.1403176.
   PubMed Web of Science ®Google Scholar
• Das A, Sinha M, Datta S, et al. Monocyte and macrophage plasticity in tissue repair and regeneration. Am J Pathol. 2015 Oct;185(10):2596–2606. doi:10.1016/j.ajpath.2015.06.001.
   PubMed Web of Science ®Google Scholar
• Krausgruber T, Blazek K, Smallie T, et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol. 2011 Mar;12(3):231–238. doi:10.1038/ni.1990.
   PubMed Web of Science ®Google Scholar
• Satoh T, Takeuchi O, Vandenbon A, et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol. 2010 Oct 22;11(10):936–944. doi:10.1038/ni.1920.
   PubMed Web of Science ®Google Scholar
• Lacey DC, Achuthan A, Fleetwood AJ, et al. Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models. J Immunol. 2012 Jun 1;188(11):5752–5765. doi:10.4049/jimmunol.1103426.
   PubMed Web of Science ®Google Scholar
• Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008 Dec;8(12):958–969. doi:10.1038/nri2448.
   PubMed Web of Science ®Google Scholar
• Juhas U, Ryba-Stanisławowska M, Szargiej P, Myśliwska J. Different pathways of macrophage activation and polarization. Postepy Hig Med Dosw (Online). 2015 Apr 22;69:496–502. doi:10.5604/17322693.1150133.
   PubMedGoogle Scholar
• Al Mamun A, Chauhan A, Yu H, Xu Y, Sharmeen R, Liu F. Interferon regulatory factor 4/5 signaling impacts on microglial activation after ischemic stroke in mice. Eur J Neurosci. 2018 Jan 1;47(2):140–149. doi:10.1111/ejn.13778.
   PubMed Web of Science ®Google Scholar
• Xie C, Liu C, Wu B, Lin Y, Ma T, Xiong H, et al. Effects of IRF1 and IFN-β interaction on the M1 polarization of macrophages and its antitumor function. Int J Mol Med. 2016 Jul;38(1):148–160. doi:10.3892/ijmm.2016.2583.
   PubMed Web of Science ®Google Scholar
• Liu Y-C, Zou X-B, Chai Y-F, Yao Y-M. Macrophage polarization in inflammatory diseases. Int J Biol Sci. 2014;10(5):520–529. doi:10.7150/ijbs.8879. PMID:24910531.
   PubMed Web of Science ®Google Scholar
• Weiss M, Blazek K, Byrne AJ, Perocheau DP, Udalova IA. IRF5 is a specific marker of inflammatory macrophages in vivo. Mediators Inflamm. 2013;2013:245804. doi:10.1155/2013/245804. PMID:24453413.
   PubMed Web of Science ®Google Scholar
• Draijer C, Robbe P, Boorsma CE, et al. Characterization of macrophage phenotypes in three murine models of house-dust-mite-induced asthma. Mediators Inflamm. 2013;2013:1–10. doi:10.1155/2013/632049.
   Google Scholar
• Byrne AJ, Weiss M, Mathie SA, et al. A critical role for IRF5 in regulating allergic airway inflammation. Mucosal Immunol. 2017 May 19;10(3):716–726. doi:10.1038/mi.2016.92.
   PubMed Web of Science ®Google Scholar
• Alzaid F, Lagadec F, Albuquerque M, et al. IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans. JCI insight. 2016 Dec 8;1(20):e88689. doi:10.1172/jci.insight.88689.
   PubMed Web of Science ®Google Scholar
• Dalmas E, Toubal A, Alzaid F, et al. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nat Med. 2015 Jun;21(6):610–618. doi:10.1038/nm.3829.
   PubMed Web of Science ®Google Scholar
• Kim D, Lee H, Koh J, et al. Cytosolic pellino-1-mediated K63-linked ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in obesity. Cell Rep. 2017 Jul 25;20(4):832–845. doi:10.1016/j.celrep.2017.06.088.
   PubMed Web of Science ®Google Scholar
• Jourdan T, Szanda G, Cinar R, et al. Developmental role of macrophage cannabinoid-1 receptor signaling in type 2 diabetes. Diabetes. 2017 Apr;66(4):994–1007. doi:10.2337/db16-1199.
   PubMed Web of Science ®Google Scholar
• Watkins AA, Yasuda K, Wilson GE, et al. IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis. J Immunol. 2015 Feb 15;194(4):1467–1479. doi:10.4049/jimmunol.1402807.
   PubMed Web of Science ®Google Scholar
• Seneviratne AN, Edsfeldt A, Cole JE, et al. Interferon regulatory factor 5 controls necrotic core formation in atherosclerotic lesions by impairing efferocytosis. Circulation. 2017 Sep 19;136(12):1140–1154. doi:10.1161/CIRCULATIONAHA.117.027844.
   PubMed Web of Science ®Google Scholar
• Peng L, Zhang H, Hao Y, et al. Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5. EBioMedicine. 2016 Dec;14:83–96. doi:10.1016/j.ebiom.2016.10.041.
   PubMed Web of Science ®Google Scholar
• Yamaguchi R, Yamamoto T, Sakamoto A, et al. A protease-activated receptor 2 agonist (AC-264613) suppresses interferon regulatory factor 5 and decreases interleukin-12p40 production by lipopolysaccharide-stimulated macrophages: role of p53. Cell Biol Int. 2016 Jun;40(6):629–641. doi:10.1002/cbin.10589.
   PubMed Web of Science ®Google Scholar
• Chionh Y-T, Ng GZ, Ong L, Arulmuruganar A, Stent A, Saeed MA, et al. Protease-activated receptor 1 suppresses helicobacter pylori gastritis via the inhibition of macrophage cytokine secretion and interferon regulatory factor 5. Mucosal Immunol. 2015 Jan 28;8(1):68–79. doi:10.1038/mi.2014.43.
   PubMed Web of Science ®Google Scholar
• Courties G, Heidt T, Sebas M, et al. In vivo silencing of the transcription factor IRF5 reprograms the macrophage phenotype and improves infarct healing. J Am Coll Cardiol. 2014;63(15):1556–1566. doi:10.1016/j.jacc.2013.11.023. PMID:24361318.
   PubMed Web of Science ®Google Scholar
• Li J, Liu Y, Xu H, Fu Q. Nanoparticle-delivered IRF5 siRNA facilitates M1 to M2 transition, reduces demyelination and neurofilament loss, and promotes functional recovery after spinal cord injury in mice. Inflammation. 2016 Oct;39(5):1704–1717. doi:10.1007/s10753-016-0405-4.
   PubMed Web of Science ®Google Scholar
• Sun K, He S-B, Qu J-G, et al. IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitisin vitro. World J Gastroenterol. 2016 Nov 14;22(42):9368–9377. doi:10.3748/wjg.v22.i42.9368.
   PubMed Web of Science ®Google Scholar
• Oriss TB, Raundhal M, Morse C, et al. IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice. JCI Insight. 2017 May 18;2(10):e91019. doi:10.1172/jci.insight.91019.
   PubMed Web of Science ®Google Scholar
• Zhu Y, Li X, Chen J, et al. The pentacyclic triterpene lupeol switches M1 macrophages to M2 and ameliorates experimental inflammatory bowel disease. Int Immunopharmacol. 2016 Jan;30:74–84. doi:10.1016/j.intimp.2015.11.031.
   PubMed Web of Science ®Google Scholar
• Zhu W, Jin Z, Yu J, et al. Baicalin ameliorates experimental inflammatory bowel disease through polarization of macrophages to an M2 phenotype. Int Immunopharmacol. 2016 Jun;35:119–126. doi:10.1016/j.intimp.2016.03.030.
   PubMed Web of Science ®Google Scholar
• Wei Z, Yan L, Chen Y, Bao C, Deng J, Deng J. Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression. Mol Med Rep. 2016 Aug;14(2):1091–1098. doi:10.3892/mmr.2016.5352.
   PubMed Web of Science ®Google Scholar
• Belz GT, Nutt SL. Transcriptional programming of the dendritic cell network. Nat Rev Immunol. 2012 Feb;12(2):101–113. doi:10.1038/nri3149.
   PubMed Web of Science ®Google Scholar
• Izaguirre A, Barnes BJ, Amrute S, et al. Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells. J Leukoc Biol. 2003 Dec;74(6):1125–1138. doi:10.1189/jlb.0603255.
   PubMed Web of Science ®Google Scholar
• Yasuda K, Richez C, Maciaszek JW, et al. Murine dendritic cell type I IFN production induced by human IgG-RNA immune complexes is IFN regulatory factor (IRF)5 and IRF7 dependent and is required for IL-6 production. J Immunol. 2007 Jun 1;178(11):6876–6885. doi:10.4049/jimmunol.178.11.6876.
   PubMed Web of Science ®Google Scholar
• Griesbeck M, Ziegler S, Laffont S, et al. Sex differences in plasmacytoid dendritic cell levels of IRF5 drive higher IFN- production in women. J Immunol. 2015 Dec 1;195(11):5327–5336. doi:10.4049/jimmunol.1501684.
   PubMed Web of Science ®Google Scholar
• Steinhagen F, McFarland AP, Rodriguez LG, et al. IRF-5 and NF-κB p50 co-regulate IFN-β and IL-6 expression in TLR9-stimulated human plasmacytoid dendritic cells. Eur J Immunol. 2013 Jul;43(7):1896–1906. doi:10.1002/eji.201242792.
   PubMed Web of Science ®Google Scholar
• Steinhagen F, Rodriguez LG, Tross D, Tewary P, Bode C, Klinman DM. IRF5 and IRF8 modulate the CAL-1 human plasmacytoid dendritic cell line response following TLR9 ligation. Eur J Immunol. 2016 Mar;46(3):647–655. doi:10.1002/eji.201545911.
   PubMed Web of Science ®Google Scholar
• Gratz N, Hartweger H, Matt U, et al. Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection. PLoS Pathog. 2011 May;7(5):e1001345. doi:10.1371/journal.ppat.1001345.
   PubMed Web of Science ®Google Scholar
• Ban T, Sato GR, Nishiyama A, et al. Lyn kinase suppresses the transcriptional activity of IRF5 in the TLR-MyD88 pathway to restrain the development of autoimmunity. Immunity. 2016 Aug 16;45(2):319–332. doi:10.1016/j.immuni.2016.07.015.
   PubMed Web of Science ®Google Scholar
• Krausgruber T, Saliba D, Ryzhakov G, Lanfrancotti A, Blazek K, Udalova IA. IRF5 is required for late-phase TNF secretion by human dendritic cells. Blood. 2010 Jun 3;115(22):4421–4430. doi:10.1182/blood-2010-01-263020.
   PubMed Web of Science ®Google Scholar
• Koch U, Radtke F. Mechanisms of T cell development and transformation. Annu Rev Cell Dev Biol. 2011 Nov 10;27(1):539–562. doi:10.1146/annurev-cellbio-092910-154008.
   PubMedGoogle Scholar
• Luckheeram RV, Zhou R, Verma AD, et al. CD4+T Cells: differentiation and functions. Clin Dev Immunol. 2012;2012:1–12. doi:10.1155/2012/925135.
   Google Scholar
• Paun A, Bankoti R, Joshi T, Pitha PM, Stäger S. Critical role of IRF-5 in the development of T helper 1 responses to leishmania donovani infection. PLoS Pathog. 2011 Jan 6;7(1):e1001246. doi:10.1371/journal.ppat.1001246.
   PubMed Web of Science ®Google Scholar
• Freitas CMT, Hamblin GJ, Raymond CM, Weber KS. Naïve helper T cells with high CD5 expression have increased calcium signaling. Houtman JCD, editor. PLoS One. 2017 May 31;12(5):e0178799. doi:10.1371/journal.pone.0178799.
   PubMed Web of Science ®Google Scholar
• Yang L, Zhao T, Shi X, et al. Functional analysis of a dominant negative mutation of interferon regulatory factor 5. PLoS One. 2009;4(5):e5500. doi:10.1371/journal.pone.0005500. PMID:19430534.
   PubMed Web of Science ®Google Scholar
• Weihrauch D, Krolikowski JG, Jones DW, et al. An IRF5 decoy peptide reduces myocardial inflammation and fibrosis and improves endothelial cell function in tight-skin mice. PLoS One. 2016;11(4):e0151999. doi:10.1371/journal.pone.0151999. PMID:27050551.
   PubMed Web of Science ®Google Scholar